International scientists worked in collaboration to identify genetic drivers of lifespan, in the largest genome wide association of lifespan to date, in which they paired genetic data from over 500,000 participants in biobanks and other cohorts with data on lifespan of each participant’s parents. Rather than studying effects of one or more elected genes on lifespan researchers looked across entire genome to answer questions in a more open ended manner and to identify new paths to explore in the future.
Effects of any given gene are statistically small, larger sample sizes are required to identify genes that are relevant to lifespan with enough weight to carry statistical power. Through using this sampling researchers were able to validate 6 previously identified associations between aging and genes such as APOE genes being linked to risk of neurodegenerative disease.
Researchers used their results to develop a polygenic risk score for lifespan: single personalized genomic score to estimate an individual’s genetic likelihood for longer life based on weighted contributions from relevant genetic variants. This polygenic risk score allowed for predictions of which participants were likely to live the longest. According to the researchers using a person’s genetic information alone the 10% of people with most protective genes can be identified who will live on average 5 years longer than the least protected 10%.
Whether genetic variants were affecting aging processes directly or affecting risk of individual diseases that could lead to death were investigated. It was found that among common variants, variants found in 1 in 200 people, those associated with Alzheimer’s, heart disease, and smoking related conditions were linked to overall lifespan; associations were not for other cancers suggesting susceptibility to death caused by other cancers is due to rare genetic variants or the environment. Some variants pertain to human history such a genetic propensity to smoking wasn’t harmful before tobacco use but is now, natural selection hasn’t had many generations to act on those variants making these variants still fairly common, explains Paul Timmers.
Examining cell types and protein pathways in which genetic variants associate with lifespan having the strongest effects lead to findings of genes playing key roles in fetal brain cells and adult prefrontal cortex cells with particular effects in pathways related to fat metabolism; highlighting the brain as an important organ in determining lifespan, and presents an opportunity for follow up studies.
Future studies will examine how the identified variants and functional pathways affect lifespan; such as investigating whether these pathways are associated with single disease with implications for longevity or a broader spectrum of age related diseases. Additional research may provides better understandings of how these interact with each other leading to possibly identifying methods to slow aging and onset of disease, improving length and quality of life.
